Date of Award

2011

Degree Type

Open Access Thesis

Document Type

Master Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Tanea T. Reed

Department Affiliation

Chemistry

Abstract

Oxidative stress has been associated in the pathogenesis of numerous diseases such as neurodegenerative disorders, ischemia, and cancer. The brain is susceptible to oxidative stress due to its high content of peroxidizable unsaturated fatty acids, high consumption of oxygen per unit weight, high levels of free radicals, and comparatively low levels of antioxidant defense systems. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can react with biomolecules such as proteins, lipids, carbohydrates, DNA, and RNA, which can lead to oxidative damage, cellular dysfunction, and can ultimately cause cell death. Down syndrome (DS) is the most common form of chromosomal abnormality found in live-born infants. DS patients have an extensive deposition of Aβ(17-42) peptide, which could contribute to their increased rate of developing Alzheimer's disease (AD). Since AD cannot be properly diagnosed until autopsy, development of a novel Down syndrome model using Aβ(17-42) could be beneficial in determining oxidative stress levels and their relationship to mild cognitive impairment (MCI), the earliest form of AD in order to possibly be used as a diagnostic tool for AD. We have found a significant difference between oxidative stress levels in Aβ(17-42) treated synaptosomes and control. By using proteomics, we have also identified several biomarkers including aldehyde dehydrogenase, aldolase, α-enolase, heat shock cognate 71, peptidyl-prolyl cis-trans isomerase, and ATP synthase α chain. Our present findings, suggest the role of Aβ(17-42) as one of the contributing factors in mediating oxidative stress in DS, and AD brain leading to neurodegeneration.

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